Name: in vivo bioluminescence imaging of tumor hypoxia dynamics of breast cancer brain metastasis in a mouse model
Uploaded: 2011-10-03T13:00:00
Description: Watch this Scientific Journal Video about In vivo Bioluminescence Imaging of Tumor Hypoxia Dynamics of Breast Cancer Brain Metastasis in a Mouse Model at JoVE.com

这项研究是支持部分由国防部乳腺癌IDEA奖W81XWH - 08 - 1 - 0583和NIH / NCI CA141348 - 01A1（DZ）和FAMRI临床科学家奖（DS）。成像的基础设施是由西南部分小动物成像研究支持计划（U24 CA126608）和西蒙斯癌症中心（P30 CA142543）和NIH 1S10RR024757 - 01。

机构动物护理和使用委员会的得克萨斯大学西南医学中心的所有动物的程序获得批准。 在体外 HIF -1α的生物发光检测1 。 <ol><li>材料和方法： <ul><li>一种新型的HIF - 1依赖记者基因转染的人类转移性乳腺癌细胞株MDA - MB231，5HRE多 - 吕克博士原田生成。 </li><li>在缺氧条件下，氧依赖性降解域（ODD）荧光素酶融合蛋白的表达增强是由5份缺氧反应元件（5HRE）。奇的存在，?...

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	<li>Harada, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+combination+of+hypoxia-response+enhancers+and+an+oxygen-dependent+proteolytic+motif+enables+real-time+imaging+of+absolute+HIF-1+activity+in+tumor+xenografts.">The combination of hypoxia-response enhancers and an oxygen-dependent proteolytic motif enables real-time imaging of absolute HIF-1 activity in tumor xenografts.</a> Biochem Biophys Res Commun. 360, 791-796 (2007).</li><li>Ou, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Usefulness+of+HIF-1+imaging+for+determining+optimal+timing+of+combining+bevacizumab+and+radiotherapy.">Usefulness of HIF-1 imaging for determining optimal timing of combining bevacizumab and radiotherapy.</a> Int J Radiat Oncol Biol Phys. 75, 463-467 (2009).</li><li>Zhou, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Dynamic+near-infrared+optical+imaging+of+2-deoxyglucose+uptake+by+intracranial+glioma+of+athymic+mice.">Dynamic near-infrared optical imaging of 2-deoxyglucose uptake by intracranial glioma of athymic mice.</a> PLoS One. 4, e8051-e8051 (2009).</li><li>Contero, A., Richer, E., Gondim, A., Mason, R. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=High-throughput+quantitative+bioluminescence+imaging+for+assessing+tumor+burden.">High-throughput quantitative bioluminescence imaging for assessing tumor burden.</a> Methods Mol Biol. 574, 37-45 (2009).</li><li>Zhao, D., Richer, E., Antich, P. P., Mason, R. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Antivascular+effects+of+combretastatin+A4+phosphate+in+breast+cancer+xenograft+assessed+using+dynamic+bioluminescence+imaging+and+confirmed+by+MRI.">Antivascular effects of combretastatin A4 phosphate in breast cancer xenograft assessed using dynamic bioluminescence imaging and confirmed by MRI.</a> FASEB J. 22, 2245-2451 (2008).</li><li>Chang, E. L., Lo, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Diagnosis+and+management+of+central+nervous+system+metastases+from+breast+cancer.">Diagnosis and management of central nervous system metastases from breast cancer.</a> Oncologist. 8, 398-410 (2003).</li><li>Palmieri, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Vorinostat+inhibits+brain+metastatic+colonization+in+a+model+of+triple-negative+breast+cancer+and+induces+DNA+double-strand+breaks.">Vorinostat inhibits brain metastatic colonization in a model of triple-negative breast cancer and induces DNA double-strand breaks.</a> Clin Cancer Res. 15, 6148-6157 (2009).</li><li>Mason, R. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Multimodality+imaging+of+hypoxia+in+preclinical+settings.">Multimodality imaging of hypoxia in preclinical settings.</a> Q J Nucl Med Mol Imaging. 54, 259-280 (2010).</li><li>Tatum, J. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hypoxia:+importance+in+tumor+biology,+noninvasive+measurement+by+imaging,+and+value+of+its+measurement+in+the+management+of+cancer+therapy.">Hypoxia: importance in tumor biology, noninvasive measurement by imaging, and value of its measurement in the management of cancer therapy.</a> Int J Radiat Biol. 82, 699-757 (2006).</li><li>Moeller, B. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pleiotropic+effects+of+HIF-1+blockade+on+tumor+radiosensitivity.">Pleiotropic effects of HIF-1 blockade on tumor radiosensitivity.</a> Cancer Cell. 8, 99-110 (2005).</li><li>Lu, X. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=In+vivo+dynamics+and+distinct+functions+of+hypoxia+in+primary+tumor+growth+and+organotropic+metastasis+of+breast+cancer.">In vivo dynamics and distinct functions of hypoxia in primary tumor growth and organotropic metastasis of breast cancer.</a> Cancer Res. 70, 3905-3914 (2010).</li><li>Zhao, D., Chang, C. H., Kim, J. G., Liu, H., Mason, R. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=In+vivo+Near-Infrared+Spectroscopy+and+Magnetic+Resonance+Imaging+Monitoring+of+Tumor+Response+to+Combretastatin+A-4-Phosphate+Correlated+With+Therapeutic+Outcome.">In vivo Near-Infrared Spectroscopy and Magnetic Resonance Imaging Monitoring of Tumor Response to Combretastatin A-4-Phosphate Correlated With Therapeutic Outcome.</a> Int J Radiat Oncol Biol Phys. 80, 574-581 (2011).</li></ol>

乳腺癌脑转移发生在IV期乳腺癌患者的30％。这是与高发病率和死亡率，并有一个中位生存期13个月6。是需要有合适的动物模型，模仿这种破坏性疾病，在临床上为了便于我们了解其颅内的启动和进展，以及病理生理型材。在这里，我们已经开发注入人类乳腺癌细胞，直接进入鼠脑，原位乳腺癌脑转移模型。我们以前的经验表明，一个放射学可视化（MRI）的颅内病变植入约2周后出现。这个...

<table border="1"><tbody><tr><th>试剂名称</th><th>公司</th><th>目录编号</th><th>评论（可选） </th></tr><tr><td> D -荧光素</td><td>黄金生物技术</td><td> L - 123 </td><td> 120毫克/公斤的PBS在体内研究的总体积80μL </td></tr><tr><td>异氟醚</td><td>巴克斯特国际公司</td><td> 1001936060 </td><td></td></tr><tr><td>基质胶</td><td> BD公司</td><td> 354234 </td><td></td></tr><tr><td>汉密尔顿注射器</td><td>汉密尔顿公司</td><td> 1701 </td><td></td></tr><tr><td> 32G汉密尔顿针</td><td>汉密尔顿公司</td><td> 7803-04 </td><td></td></tr><tr><td>低氧室</td><td>比卢普斯罗森堡，公司</td><td> MIC - 101 </td><td></td></tr><tr><td>生物发光成像系统</td><td>卡尺生命科学</td><td> IVIS光谱系统</td><td></td></tr><tr><td> G418 </td><td> Fisher Scientific则</td><td> SV3006901 </td><td></td></tr></tbody></table>

in vivo bioluminescence imaging of tumor hypoxia dynamics of breast cancer brain metastasis in a mouse model

众所周知，肿瘤的缺氧起着促进恶性进展和治疗反应产生负面影响重要作用。有一点知识在原地，在体内 ，在缺氧的发展，因为缺乏有效的手段来监测这些深层次的原位肿瘤恶性脑肿瘤的颅内肿瘤，。生物发光成像（劳保局），表达的荧光素酶基因的活细胞所发出的光检测的基础上，已迅速采用为癌症研究，特别是评估肿瘤的生长或应对，在临床前动物研究治疗肿瘤的大小变化。此外，通过一个控制下的一个子序列的记者基因表达，特定的基因表达是可以被监测的非侵入性劳保局。缺氧压力下，主要通过缺氧诱导因子-1α（HIF -1α）介导的信号反应，以驱动各种基因的转录。因此，我们必须使用一个记者HIF -1α建设，5HRE多- LUC，稳定转染人乳腺癌MDA - MB231 细胞在体外HIF -1α的生物发光检测（MDA-MB231/5HRE-ODD-luc）是由孵化在低氧室，24小时前劳保局（0.1％O 2）转染的细胞，而细胞在常氧（21％O 2）作为一个控制。显着较高的光子通量细胞缺氧条件下的观察表明其启动的增加HIF -1α结合（HRE元素），比在常氧。细胞是直接注射到老鼠大脑建立一个乳腺癌脑转移瘤模型，在体内的肿瘤乏氧动力学生物发光成像。植入后2周开始，并反复每周一次。劳保局揭示增加脑肿瘤进展的光信号，表明增加了颅内肿瘤缺氧。组织学及免疫组织化学研究，以确认在体内成像结果。在这里，我们将介绍在体外 HIF -1α的生物发光检测，乳腺癌裸鼠和应用，在体内的生物发光成像技术来监测颅内肿瘤缺氧的脑转移瘤的手术建立的方法。

Watch this Scientific Journal Video about In vivo Bioluminescence Imaging of Tumor Hypoxia Dynamics of Breast Cancer Brain Metastasis in a Mouse Model at JoVE.com

In vivo Bioluminescence Imaging of Tumor Hypoxia Dynamics of Breast Cancer Brain Metastasis in a Mouse Model

缺氧诱导因子-1α活动的生物发光成像是用于监测在乳腺癌脑转移瘤小鼠模型的颅内肿瘤缺氧发展。

在小鼠模型体内生物发光成像乳腺癌脑转移的肿瘤乏氧动力学

It is well recognized that tumor hypoxia plays an important role in promoting malignant progression and affecting therapeutic response negatively. There ...

Research

JoVE Journal

Medicine

In vivo Bioluminescence Imaging of Tumor Hypoxia Dynamics of Breast Cancer Brain Metastasis in a Mouse Model

Multi-photon Imaging of Tumor Cell Invasion in an Orthotopic Mouse Model of Oral Squamous Cell Carcinoma

多光子成像在口腔鳞状细胞癌原位小鼠模型的肿瘤细胞的侵袭

Loco-regional invasion of head and neck cancer is linked to metastatic risk and presents a difficult challenge in designing and implementing patient ...

科研

医学

Combination Radiotherapy in an Orthotopic Mouse Brain Tumor Model

在原位小鼠脑肿瘤模型结合放疗

Glioblastoma multiforme (GBM) are the most common and aggressive adult primary brain tumors1. In recent years there has been substantial progress in the ...

Stereotactic Intracranial Implantation and In vivo Bioluminescent Imaging of Tumor Xenografts in a Mouse Model System of Glioblastoma Multiforme

Stereotactic Intracranial Implantation and In vivo Bioluminescent Imaging of Tumor Xenografts in a Mouse Model System of Glioblastoma Multiforme

立体定向颅内植入和<em在体内</em生物发光成像的肿瘤异种移植的小鼠模型系统的多形性胶质母细胞瘤

Glioblastoma multiforme (GBM) is a high-grade primary brain cancer with a median survival of only 14.6 months in humans despite standard tri-modality ...

Multi-modal Imaging of Angiogenesis in a Nude Rat Model of Breast Cancer Bone Metastasis Using Magnetic Resonance Imaging, Volumetric Computed Tomography and Ultrasound

利用磁共振成像，容积电脑断层扫描及超音波的裸鼠乳腺癌骨转移大鼠模型血管生成的多模态成像

Angiogenesis is an essential feature of cancer growth and metastasis formation. In bone metastasis, angiogenic factors are pivotal for tumor cell ...

Screening for Melanoma Modifiers using a Zebrafish Autochthonous Tumor Model

对黑色素瘤修饰符一个斑马鱼原地肿瘤模型的筛选

Genomic studies of  human cancers have yielded a wealth of information about genes that are altered  in tumors1,2,3. A challenge arising from these ...

Live Imaging of Drug Responses in the Tumor Microenvironment in Mouse Models of Breast Cancer

实时成像在乳腺癌小鼠模型中的肿瘤微环境对药物的反应

The tumor microenvironment plays a pivotal role in tumor initiation, progression, metastasis, and the response to anti-cancer therapies. Three-dimensional ...

Time-lapse Imaging of Primary Preneoplastic Mammary Epithelial Cells Derived from Genetically Engineered Mouse Models of Breast Cancer

延时成像的主要癌前乳腺上皮细胞来源于遗传工程小鼠乳腺癌模型

Time-lapse  imaging can be used to compare behavior of cultured primary preneoplastic  mammary epithelial cells derived from different genetically ...

A Novel High-resolution In vivo Imaging Technique to Study the Dynamic Response of Intracranial Structures to Tumor Growth and Therapeutics

A Novel High-resolution In vivo Imaging Technique to Study the Dynamic Response of Intracranial Structures to Tumor Growth and Therapeutics

一种新型的高分辨率<em&gt;在体内</em&gt;成像技术研究肿瘤生长及治疗颅内结构的动态响应

We have successfully integrated previously established Intracranial window (ICW) technology 1-4 with intravital 2-photon confocal microscopy to develop a ...

Ultrasound Imaging-guided Intracardiac Injection to Develop a Mouse Model of Breast Cancer Brain Metastases Followed by Longitudinal MRI

超声成像引导下腔内注射到患乳腺癌脑转移其次是纵向的MRI的小鼠模型

Breast cancer brain metastasis, occurring in 30% of breast cancer patients at stage IV, is associated with high mortality. The median survival is only 6 ...

Initiation of Metastatic Breast Carcinoma by Targeting of the Ductal Epithelium with Adenovirus-Cre: A Novel Transgenic Mouse Model of Breast Cancer

乳腺癌的一种新的转基因小鼠模型：转移性乳腺癌通过瞄准导管上皮与腺病毒Cre重组酶的启动

Breast cancer is a heterogeneous disease involving complex cellular interactions between the developing tumor and immune system, eventually resulting in ...